Epigenetic regulation is a process that takes place through adaptive cellular pathways influenced by environmental factors and metabolic changes to modulate gene activity with heritable phenotypic variations without altering the DNA sequences of many target genes. Epigenetic regulation can be facilitated by diverse mechanisms: many different types of post-translational modifications (PTMs) of histone and non-histone nuclear proteins, DNA methylation, altered levels of noncoding RNAs, incorporation of histone variants, nucleosomal positioning, chromatin remodeling, etc. These factors modulate chromatin structure and stability with or without the involvement of metabolic products, depending on the cellular context of target cells or environmental stimuli, such as intake of alcohol (ethanol) or Western-style high-fat diets. Alterations of epigenetics have been actively studied, since they are frequently associated with multiple disease states. Consequently, explorations of epigenetic regulation have recently shed light on the pathogenesis and progression of alcohol-associated disorders. In this review, we highlight the roles of various types of PTMs, including less-characterized modifications of nuclear histone and non-histone proteins, in the epigenetic regulation of alcohol-associated liver disease (ALD) and other disorders. We also describe challenges in characterizing specific PTMs and suggest future opportunities for basic and translational research to prevent or treat ALD and many other disease states.

表观遗传调控是通过受环境因素和代谢变化影响的适应性细胞途径发生的过程，以可遗传的表型变异调节基因活性，而不改变许多靶基因的DNA序列。表观遗传调控可以通过多种机制来促进：组蛋白和非组蛋白核蛋白的许多不同类型的翻译后修饰 (PTM)、DNA 甲基化、非编码 RNA 水平的改变、组蛋白变体的掺入、核小体定位、染色质重塑等这些因素在有或没有代谢产物参与的情况下调节染色质结构和稳定性，具体取决于靶细胞的细胞背景或环境刺激，例如酒精（乙醇）或西式高脂肪饮食的摄入。表观遗传学的改变已被积极研究，因为它们经常与多种疾病状态相关。因此，对表观遗传调控的探索最近揭示了酒精相关疾病的发病机制和进展。在这篇综述中，我们重点介绍了各种类型的 PTM 在酒精相关性肝病 (ALD) 和其他疾病的表观遗传调控中的作用，包括核组蛋白和非组蛋白的特征较少的修饰。我们还描述了表征特定 PTM 的挑战，并提出了预防或治疗 ALD 和许多其他疾病状态的基础和转化研究的未来机会。